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Oxidatively modified, mitochondria-relevant brain proteins in subjects with Alzheimer disease and mild cognitive impairment

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Abstract

Alzheimer disease (AD) is an age-related neurodegenerative disorder, characterized histopathologically by the presence of senile plaques (SP), neurofibrillary tangles and synapse loss in selected brain regions. Positron emission tomography (PET) studies of glucose metabolism revealed decreased energetics in brain of subjects with AD and arguably its earliest form, mild cognitive impairment (MCI), and this decrease correlated with brain structural studies using MRI. The main component of senile plaques is amyloid beta-peptide (Aβ), a 40–42 amino acid peptide that as oligomers is capable of inducing oxidative stress under both in vitro and in vivo conditions and is neurotoxic. In the mitochondria isolated from AD brain, Aβ oligomers that correlated with the reported increased oxidative stress markers in AD have been reported. The markers of oxidative stress have been localized in the brain regions of AD and MCI that show pathological hallmarks of this disease, suggesting the possible role of Aβ in the initiation of the free-radical mediated process and consequently to the build up oxidative stress and AD pathogenesis. Using redox proteomics our laboratory found a number of oxidatively modified brain proteins that are directly in or are associated with the mitochondrial proteome, consistent with a possible involvement of the mitochondrial targeted oxidatively modified proteins in AD progression or pathogenesis. The precise mechanistic link between mitochondrial oxidative damage and role of oligomeric Aβ has not been explicated. In this review, we discuss the role of the oxidation of mitochondria-relevant brain proteins to the pathogenesis and progression of AD.

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Authors and Affiliations

  1. Department of Chemistry, University of Kentucky, Lexington, KY, 40506-0055, USA

    Rukhsana Sultana & D. Allan Butterfield

  2. Center of Membrane Sciences, University of Kentucky, Lexington, KY, 40506-0059, USA

    Rukhsana Sultana & D. Allan Butterfield

  3. Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, 40536, USA

    Rukhsana Sultana & D. Allan Butterfield

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  1. Rukhsana Sultana
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  2. D. Allan Butterfield
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Correspondence to D. Allan Butterfield.

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Sultana, R., Butterfield, D.A. Oxidatively modified, mitochondria-relevant brain proteins in subjects with Alzheimer disease and mild cognitive impairment. J Bioenerg Biomembr 41, 441–446 (2009). https://doi.org/10.1007/s10863-009-9241-7

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